抗癌剤の現状と将来.特に生薬薬理の観点から
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概要
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The most important problem in cancer research is to increase comfortably the survival time and to prevent completely recurrence after surgical resection in cancer patients. Cytocidal anticancer chemotherapeutics have detrimental side effects and destroy host defence mechanisms, and are not useful for cancer patients. On the other hand, there is several evidence suggesting the existence of intrinsic resistance to cancer. The examples are an equilibrium state with proliferation and regression in a small amount of cancer cells and spontaneous regression of cancer. An increase in this resistance may be one of the most important problem to find new anticancer drugs. In Oriental medicine practiced in Asian countries from olden times, the fundamental principle is to regulate homeostasis of the whole body and to bring the diseased person to a normal state, rather than to attack the focus directly. On the basis of such a concept, the antitumor activity of numerous folk remedies has been reexamined and isolated a polysaccharide with marked antitumor activity and named as lentinan. Lentinan is a strictly purified β-1,6 : β-1,3-D-glucan, and exerts prominent antitumor activities in murine allogeneic, syngeneic and autochthonous hosts, prevents chemical and viral oncogeneses, and suppresses tumor metastasis in several clinical models. The antitumor action of lentinan is host-mediated. Comparing with other well-known immunostimulants, such as BCG, C. parvum and LPS, lentinan appears to represent a unique class of immunopotentiator, a T-cell oriented adjuvant in which macrophages play some parts. First, lentinan triggers the increased production of various kinds of bioactive serum factors associated with immunity and inflammation, such as CSF, IL-1,IL-3,vascular dilatation hemorrhage inducer and acute-phase protein inducer, by direct impact of macrophages or indirectly via lentinan-stimulated T-cells, which results in the induction of many immunobiological changes in the host. Augmented IL-1 production amplifies the maturation of immature effector cells to mature cells capable of responding to IL-2 and other cytokines, but lentinan do not augment production of IL-2. This is the most important characteristics of lentinan, because this suggests a contact point between new immunology and Oriental medicine. Lentinan augments differentiation of various kinds of important cells in the host defence. These results clearly explain the requirment of intact macrophages and T-cell compartments for antitumor activity of lentinan. Lentinan has only a little toxic side effect in in vivo application to animals and human. An excellent result was obtained in 4 year's follow-up of the randomized control study of lentinan in Phase III on the patients with advanced and recurrent stomach, colo-rectal, breast cancer and malignant lymphoma. These results suggest that lentinan might be more effective for micrometastasis after surgery. Lentinan is a hopeful drug for cancer patients.
- 社団法人日本薬学会の論文
- 1988-03-25